Method and apparatus for controlled reoxygenation

ABSTRACT

A method and apparatus for performing coronary perfusion and cardiac reoxygenation that enables accurate control of oxygen levels in blood used for the coronary circulation. Deoxygenated blood and oxygenated blood are collected and oxygen levels are measured by sensors. The deoxygenated and oxygenated blood is then mixed and the mixed blood is measured by another sensor. The sensors provide data used to provide real-time oxygen level measurement and adjustment for blood supplied for coronary circulation.

RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application Ser.No. 60/511,837 filed Oct. 16, 2003, the entirety of which isincorporated by reference.

GENERAL

The present invention relates to medical devices for use in heartsurgery. In particular, the present invention pertains to a method andapparatus for controlled coronary perfusion and/or cardiacreoxygenation.

During a heart operation, the functions of a patient's heart and lungsare often bypassed through cardiopulmonary bypass (CPB) equipment, alsoknown as a heart-lung machine. The heart-lung machine's main circuit, inessence, consists of a pump (to replace the functions of the heart) andan oxygenator (to replace the function of the lungs). When connected tothe patient by way of large insertion tubes known as cannulae, theheart-lung machine completes a continuous tubing circuit in which carbondioxide is removed from the patient's blood, oxygen is added, and thereoxygenated blood is pumped back into the patient's body, usuallythrough the aorta or one of its major braches.

The heart-lung machine drains deoxygenated, venous (blue) blood from theright atrium of the patient's heart or from one or both vena cavae intoa reservoir. From the reservoir, the deoxygenated blood is pumpedthrough an oxygenator. The oxygenator, usually by way of a multiplehollow-fiber membrane, exposes the blood to gaseous oxygen. Due todissolution and a direct biochemical reaction between hemoglobin andoxygen molecules, the blood becomes oxygenated. The oxygenated blood(red blood) is then pumped back into the body through an artery,typically, the aorta or one of its major branches.

The heart-lung machine also routinely perform the tasks of salvagingshed blood that leaves the circulation through the surgical wound oropen cardiac chambers, cooling or heating of the blood and, therefore,the patient, or introduction of medications directly into the bloodstream. Gaseous anesthetic agents or room air may also be introduced viathe oxygenator.

During cardiopulmonary bypass (CPB), cardioplegia is typically used toprotect and, in some situations, resuscitate the heart. Cardioplegia istypically a combination of blood and saline (crystalloid) solution withvarious components used to stop the heart's electrical and, ultimately,its mechanical activity. The cardioplegia circuit comprises tubing, aseparate pump or pump head, and a mixing system that controls the ratioof crystalloid to blood delivered to the heart (typically 1:3 or 1:4). Astandard cardioplegia circuit allows for either streaming oxygenatedblood from the oxygenator to mix with a crystalloid solution in apre-specified ratio or for the pooling of blood in a reservoir;therefore allowing dilution with the crystalloid within the reservoir ina given ratio. The oxygenated blood and crystalloid cardioplegiamixture, typically known as a “perfusate” or a “reperfusate” is thenapplied to the heart. The reperfusate, or cardioplegic solution,includes varying concentrations of potassium chloride that arrests theheart. Because the reperfusate also applies oxygenated blood to theheart tissues via the coronary circulation, the arrested heart continuesto receive oxygen during the arrest phase or cardioplegia phase of acardiac operation. This ongoing oxygen delivery to the arrested hearttypically occurs at least intermittently; however with some perfusionstrategies, it may occur continuously or almost continuously.

For myocardial protection, a surgeon separates the blood supply sent tothe aorta (or another major branch) for total body perfusion and theblood supply sent to the coronary circulation (via the aortic root, thecoronary sinus or previously constructed bypass grafts). In so doing,the heart surgeon limits the amount of oxygen to which the heart isexposed and can precisely control other components of the coronaryperfusate by designing a cardioplegia solution that contains protectivenutrients for cardiac resuscitation and protection when the heart is cutoff from the perfusion of the rest of the body. Circulation to theremainder of the patient's body is controlled by the perfusionist andthe anesthesiologist working in concert to ensure, in particular, therequired amount of oxygenation that must be provided to the patient'sbrain, kidneys, liver and other major organ systems. Accordingly,significantly high levels of oxygen are present in the blood used fortotal body perfusion. In typical CPB equipment, including thecardioplegia circuit, the coronary circulation is exposed to the samelevels of oxygen.

The standard cardioplegia circuit approach, however, may lead toreperfusion injury especially for patients in whom ongoing or antecedentmyocardial tissue ischemia (an unfavorable imbalance between the demandof oxygen and the supply of oxygen) is present prior to commencing thesurgical procedure or prior to commencing CPB and cardioplegic arrest.Variable degrees of surgically induced ischemia may also develop, whilethe heart is arrested during surgery and receiving oxygenintermittently, that can predispose to reperfusion injury as well. Toillustrate this point, it has been shown, experimentally and in clinicalsituations, that uncontrolled or abrupt oxygen re-exposure is injuriousin a number of situations in which hypoxic cardiac(myocardial/conduction/endothelial) tissue is present. Examples mightinclude children with complex congenital heart lesions leading tocyanosis or adult patients with unstable coronary syndromes that havebeen clinically protracted.

Reperfusion injury comprises a number of different and importantcellular and molecular processes that amplify or aggravate an ischemicinsult. During a period of a variable degree of ischemia (when bloodflow and, therefore, oxygen delivery to one or more areas of the heartis limited), the affected cells undergo alterations from aerobic toanaerobic metabolism. As the intensity and/or duration of the ischemiaincrease, the affected tissues can become overwhelmed by reperfusion andthe reintroduction of oxygen when and if it occurs. The paradox lies inthe realization that while the restoration of the availability of oxygen(and blood flow) is ultimately necessary to restore tissue integrity andinsure survival, under certain conditions, this can also be detrimental.If reperfusion can be established after only brief or relatively mildconditions of ischemia, the tendency toward cell injury is reduced andnatural restorative processes can and do reverse the ischemic injury.

Increasing degrees of reversible ion (sodium, potassium, calcium)dys-homeostasis or imbalance across the cell and mitochondrial membranesbegin to develop during the early stages of an ischemic insult andworsen or progress with time and with increasing intensity of theischemia. In other words, as ischemic conditions progress, the cellsdevelop ion shifts that lead to increasingly unfavorable conditions. Ifflow and oxygen delivery are suddenly reestablished, the affectedtissue/cells can be overwhelmed by unfavorable ion flux (mostimportantly, calcium influx), pressure alterations and pH changes thatultimately lead to explosive cell injury and death by several differentmechanisms. The re-exposure of the milieu to molecular oxygen and theresultant re-energization of the cell lead to contraction necrosis dueto calcium overload in the worst-case scenario. Less severe forms ofcalcium overload can lead to rigor contracture also leading toincremental cellular dysfunction and injury.

Cyanotic conditions imply normal flow of deoxygenated blood, andischemic conditions imply lack of flow of normally oxygenated blood. Atthe tissue level, however, overwhelming oxidative stress has been shownto be dangerous in both settings, albeit by somewhat differentmechanisms. Significant degrees of oxidative stress lead to theformation of highly reactive and injurious molecules that are formed bythe addition of oxygen into an unfavorable milieu. An example of thiswould be the formation of peroxynitrite after reoxygenation of cyanotictissues, which may adapt to such conditions by producing increasinglevels of nitric oxide (caused by the increased activity of endothelialcell derived inducible nitric oxide synthetase [iNOS]). The presence ofsuch molecules after reoxygenation leads to cellular injury through aprocess known as lipid peroxidation in which the cell membrane lipidbilayer is attacked and rendered permeable or worse. Such cell membranedamage can lead to cellular destruction, which is additive after aprevious ischemic insult and which has been shown to be very poorlytolerated after cyanosis. This is particularly true in cyanotic childrenwho are abruptly reoxygenated on CPB during surgery to correct oftencomplex congenital heart lesions.

Finally, we are becoming aware of a number of other mechanisms by whichreperfusion injury can aggravate cellular or tissue injury followingischemia. Such transcriptionally related events add an increment ofcellular death and tissue dysfunction much later (days to weeks) afterthe initial insult. These events relate to the activation of theinflammatory pathways, the release of cytokines, upregulation ofintracellular transcription factors (like nuclear factor Kappa B). Eachcontributes to adhesion of leukocytes and the resultant inflammatoryinjury and programmed cell death (apoptosis) can also be activated bythe transcription of several apoptosis genes that have been identified.

Recent preliminary research data suggests that all of the processesdiscussed above can be favorably altered by controlled reoxygenation.Plausible hypotheses have been offered for favorably manipulating theseprocesses. The clinical work has shown promise that the concept ofcontrolled reoxygenation in adult cardiac surgery improves theprotection of the previously ischemic heart from injury. The reperfusionof the adult human heart with venous blood cardioplegia in a clinicalsetting has been described and also shown a survival benefit in ananimal experiment designed to exploit the fatal nature of overwhelmingreperfusion injury under certain circumstances. This demonstrates that areduction in oxidative stress at the time of controlled reperfusionafter particularly severe ischemia is, indeed, protective. This may workby lowering the gradient of oxygen delivery during initial reperfusionto the previously hypoxic areas allowing time for improved ionhomeostasis (prior to re-exposure to molecular oxygen), and reducing thetendency for the cells to experience calcium overload resulting incontraction necrosis (one form of reperfusion injury). A brief period ofdeoxygenated blood/cardioplegic reperfusion followed by a gradualincrease of re perfusate pO₂ can also reduce lipid peroxidation ofcellular membranes; another immediate form of reperfusion injury.

In order to control cardiac reoxygenation, perfusionists (techniciansthat operate the heart-lung machine) have spliced a line of tubing intothe cardioplegia circuit of a heart-lung machine that allows venousblood to be pumped through the cardioplegia circuit to the heart toexploit this enhanced protection. Oxygen levels have been lowered tomore physiologic ranges. In the case of ischemic myocardial tissue, thismeans exposure of the heart to pO₂'s in the venous range, graduallyraising the pO₂ by mixing arterial and venous blood and by eventuallyallowing only arterial blood to the heart. In addition, the percentageof oxygen exposed directly to the membrane oxygenator has been reduced.By adding a tank of room air to the circuit, an air-oxygen mixture isachieved such that the resultant blood pO₂ is more acceptable and morephysiologic at all points while CPB is used in any given patient(cyanotic child, adult with coronary heart disease or any othersituation).

While real time read-outs of blood or cardioplegia circuit pO₂ areavailable, the pO₂ of sanguineous cardioplegia is typically notconsidered. Further, the splicing arrangement that I have pioneered islimited in its ability to precisely control and adjust the the pO₂ ofblood cardioplegia. Accordingly, abrupt changes from deoxygenated bloodto oxygenated blood are possible under the splicing arrangement. Assuch, difficulties exist in providing controlled reoxygenation due to alack of precision in the adjustment and real-time measurement of oxygenlevels in the blood provided to the coronary circulation.

BRIEF SUMMARY

The presently preferred embodiments are directed toward a stand-alonedevice or component of another device or system that controlsoxygenation levels of blood presented for reintroduction to the humanbody and, in particular, the human heart. As noted above, for a numberof reasons it may be desirable to control oxygen levels for coronaryreperfusion after ischemia in an effort to control cardiac reoxygenationand to mitigate additive injury that occurs under certain conditions.

By utilizing the tube splicing technique described above and with theaorta and the coronary circulations separated by a clamp, separateoxygenation levels have been achieved and thus provided to the bodythrough the aorta (or other major branch) and to the heart. The surgeoncan, under these circumstances, but to only a certain degree, controlcardiac reoxygenation. The method is problematic, however, because itdoes not provide for an accurate way to precisely control theoxygenation levels of blood in real-time. The surgeon and theperfusionist working together guess at the actual levels of blood pO₂.Further, while blood gas determinations can be obtained during suchcontrolled reperfusion attempts, the data is delayed and real-timeadjustments are, at best, difficult and approximate.

The presently preferred embodiments improve upon the splicingtechniques. A presently preferred embodiment utilizes blood from thevenous reservoir and from an oxygenator and allows for precise mixingand a real-time read out of blood pO₂ levels. Cardiopulmonary bypasstubing from the venous reservoir and arterial (post-oxygenator) linesfeed the system to allow mixing of desaturated and arterialized bloodfrom the bypass circuit. In a presently preferred embodiment, sensorsmeasure the oxygen saturation and pO₂ levels of incoming blood receivedfrom the oxgenator, venous blood received from the patient, and outgoingmixed blood used for coronary perfusion.

In one embodiment, a microprocessor (or a combination ofmicroprocessors) receives the data from the sensors and providesfeedback to the surgeon and/or perfusionist. In another embodiment, thisdata is used by the microprocessor to control the pump heads within thesystem, providing adjustments to the venous and arterial mixture.

Oxygenators may not necessarily provide entirely consistent results inoxygen saturation or pO₂, and, in particular, may provide differentresults on a patient-by-patient basis and from time to time within thesame patient. The presently preferred embodiments seek to provide asubstantially constant level of oxygen that is sent through the systemfor coronary perfusion that is also continuously adjustable. Theseadjustments may be set by the perfusionist and controlled within thesystem through the microprocessors management of data collected by thesensors. Thus, despite potential variation in the oxygen levels, e.g.partial pressures, of the oxygenated blood exiting the oxygenator and inthe venous reservoir, the blood pumped to the coronary circulation maybe accurately regulated.

The microprocessor may receive further direction to adjust (up or down)the pO₂ of the output blood. This direction may be controlled and/orprogrammed by a dial, digital read-out, or touch screen of desiredlevels of oxygen within the admixture of blood from the venous andarterial sides of the pump that the surgeon or perfusionist may selectfor any given situation. In this regard, the microprocessor may controlthe internal pump heads, reservoir, and/or internal bladders to providea real-time adjustment of the oxygen level in the blood pumped to thecoronary circulation.

In a first aspect, a perfusion control input receives a desired bloodoxygen level, a venous blood sensor measures oxygen levels in venousblood, an oxygenated blood sensor measures oxygen levels in oxygenatedblood, a mixed blood supply receives venous blood and oxygenated blood,and a mixed blood sensor measures oxygen levels in the mixed bloodsupply. Venous and oxygenated blood pumps are provided to move venousand oxygenated blood, respectively. A microprocessor receives data fromthe perfusion control input and the sensors and instructs the pumps toincrease, decrease, or completely stop, blood flow to reach the desiredblood oxygen level.

In a second aspect, a venous drainage pathway, a systemic perfusionpathway, and cardioplegia delivery pathway are provided. An oxygenatoris connected with the venous drainage pathway and has one or moreoutputs connected with the systemic delivery pathway and an oxygenationcontroller. The oxygenation controller reads data from at least oneblood oxygen level sensor and mixes blood from the venous drainagepathway and systemic delivery pathway to create a mixed blood supply.

In a third aspect, a venous blood supply, an oxygenated blood supply, atleast one sensor for measuring blood oxygen levels, and a desiredoutputted blood oxygen level are provided. Blood from the venous bloodsupply is mixed with blood from the oxgyenated blood supply. Bloodoxygen level data is collected. The mixed blood oxygen level is thencompared with the desired blood oxygen level and the mixture of blood isadjusted in response to the comparison.

In a fourth aspect, a microprocessor is provided with one or morememories operable to store data corresponding to a real-time bloodoxygen level for deoxygenated blood, data corresponding to a real-timeblood oxygen level for oxygenated blood, data corresponding to areal-time blood oxygen level corresponding to a mixture of deoxygenatedand oxygenated blood, and data corresponding to a desired blood oxygenlevel for the mixture of deoxygenated and oxygenated blood. Themicroprocessor controls the amount of deoxygenated and oxygenated bloodprovided to the mixture of deoxygenated and oxygenated blood.

In a fifth aspect, deoxygenated and oxygenated blood supplies areprovided. The deoxygenated blood supply may be venous blood or anothersource of blood with oxygen levels that are lower than the oxygenatedblood supply. The oxygenated blood supply may be blood that has passedthrough an oxygenator or another source of blood with oxygen levels thatare higher than the deoxygenated blood. The oxygen levels may be, forexample, partial pressure of oxygen or oxygen saturation. Real-timeblood oxygen level and flow rate data for the deoxygenated blood andreal-time blood oxygen level and flow rate data for the oxygenated bloodis received. Blood from the dexogyenated blood supply is mixed withblood from the oxygenated blood supply. Real-time blood oxygen leveldata for the mixed blood is received and flow rates of the oxygenatedblood and/or deoxygenated blood are adjusted.

In a sixth aspect, a perfusion control input, a venous blood supplyinput, an oxygenated blood supply input, and a mixed blood lineconnected with the venous blood supply and oxygenated blood supplyinputs are provided. A mixed blood sensor measures blood oxygen levelsin the mixed blood line and a microprocessor receives data from theperfusion control input and mixed blood sensor and controls the mixtureof the venous blood with the oxygenated blood.

In a seventh aspect, reservoirs are provided to hold deoxygenated blood,oxygenated blood, and a mixture of deoxygenated and oxygenated blood forcoronary circulation. Sensors are provided to measure oxygen levels ineach of the reservoirs.

In an eighth aspect, blood lines are provided to hold deoxygenatedblood, oxygenated blood, and a mixture of deoxygenated and oxygenatedblood for coronary circulation. Sensors are provided to measure oxygenlevels in each of the blood lines.

In a ninth aspect, blood supplies are provided to hold deoxygenatedblood, oxygenated blood, and a mixture of deoxygenated and oxygenatedblood for coronary circulation. At least one sensor measures oxygenlevels of the blood in the mixture of deoxygenated and oxygenated blood.

The presently preferred embodiments may enable the operator to providemore accurate oxygenation levels for cardiac circulation and controlledreoxygenation of the human heart during resuscitation. The use of thepreferred embodiments may, in particular, improve the protection of theactively ischemic heart or the heart of cyanotic patients.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a block diagram of a standard cardiopulmonary bypass (CPB)circuit.

FIG. 2 is a block diagram of a cardiopulmonary bypass (CPB) circuitincorporating one embodiment.

FIG. 3 is a block diagram of a cardiopulmonary bypass (CPB) circuitincorporating another embodiment.

FIG. 4 is a block diagram of another embodiment of a cardiopulmonarybypass circuit.

FIG. 5 is a flowchart depicting microprocessor control of oxygenationlevels for cardiac circulation in accordance with one embodiment.

DETAILED DESCRIPTION OF THE DRAWINGS AND THE PRESENTLY PREFERREDEMBODIMENTS

FIG. 1 illustrates the prior art of the typical cardiopulmonary bypasscircuit 100. The patient 110 has cannulae connected to differentstructures of the heart (or great vessels) for drainage and appropriateperfusion that are in turn connected to the tubing of the CPB circuit.The CPB circuit receives drainage from the right heart 112, deliversoxygenated blood to the aorta (or other major branch) 114 and deliverscardioplegia for coronary circulation 116. The venous drainage pathway120 receives blood from right atrium, great veins (i.e., the inferiorand superior vena cavae) or both for venous drainage via venous cannula(or cannulae) and a variable length of tubing. The blood received in thevenous pathway 120 is then collected in a blood reservoir 122. Thereservoir 122 is typically open (or vented) to the atmosphere, but maybe closed, and briefly stores the deoxygenated blood. A pump head 126pumps the deoxygenated blood through the circuit's tubing 124 to ahollow fiber membrane oxygenator 130. The oxygenator 130 may eliminatecarbon dioxide and/or other waste products from the blood and providesoxygen by exposure of the membrane to a supply of oxygen typically givenas either pure gaseous oxygen or mixed with a supply of room air.

As one skilled in the art would appreciate, the oxygenator 130 may takeseveral different forms. For example, the oxygenator 130 may also be abubble or membrane oxygenator. Similarly, the pump 126 may comprise avariety of different types of pumps. For example, a roller pump orcentrifugal pump, in which the speed of the spinning head (and theresistance of the system) determines the flow of blood or perfusate, maybe used.

Upon exiting the oxygenator 130, oxygenated blood is sent through thesystemic perfusion pathway 132. The systemic perfusion pathway 132connects with the aortic cannula (not shown), which in turn connectswith the aorta (or other major branch) 114. The systemic perfusionpathway 132 typically includes a length of tubing and a filter thattraps small particles and microbubbles (not shown). The flow of theoxygenated blood to the systemic pathway 132 is controlled by the pump126.

In a typical cardiopulmonary bypass set up, a portion of the oxygenatedblood is also sent through the cardioplegia circuit 140, whichcirculates a blood-crystalloid mixture to the heart itself. Thecardioplegia portion 140 of the circuit 100 includes a length of tubing142 that connects the oxygenator 130 to a cardioplegia delivery system144. The cardioplegia delivery system 144 mixes the blood andcrystalloid to form the cardioplegia. Connected to the cardioplegiadelivery system 144 is a cardioplegia delivery pathway 146 that deliverscardioplegia to the coronary circulation 116. The delivery ofcardioplegia through the cardioplegia delivery pathway 146 is typicallyaccomplished through an antegrade cardioplegia needle inserted into theaortic root, a retrograde cardioplegia catheter inserted into thecoronary sinus, a handheld cardioplegia catheter that can be insertedinto the coronary ostium, or a combination thereof.

Cardioplegia systems include systems in which a predetermined and/orconsistent blood-crystalloid ratio perfusate is delivered throughout theprocedure, but may include more complex systems in which subtlealterations in blood-crystalloid ratios can be effected and in whichpharmacologic agents (drugs) can be administered in a very precisemanner. To administer cardioplegia to the heart (coronary circulation),blood is generally mixed in a 3:1 or 4:1 ratio with a crystalloidsolution, which stops the heart when applied through the cardioplegiadelivery pathway 146. In the alternative, a blood and crystalloid mixingsystem or reservoir 144 is an integrated cardioplegia delivery system.Such systems allow for control over a number of factors involved incardioplegia delivery. For example, precise ratios of blood tocrystalloid can be dialed in and medication adjustments can be preciselycontrolled allowing for the administration of things like insulin,adenosine or other drugs.

FIG. 2 shows a block diagram of a cardiopulmonary bypass circuit 200utilizing an embodiment of a cardioplegia circuit. The circuit 200includes an oxygenation controller 210. The oxygenation controller 210is a microprocessor, a general processor, a controller, an applicationspecific intergrated circuit, a transistor, a field programmable gatearray, an analog circuit, a digital circuit, valves, pumps, filters,tubing, a reservoir or bladder or a series of the same, relays, sensors,pulse oximetry sensors, combinations thereof or other now known or laterdeveloped devices for mixing fluids from two different sources by usingdata relating to partial pressure of oxygen, oxygen saturation, oroxygen content or level in the fluids. The oxygenation controller 210 isconnected with tubing 220, which carries oxygenated blood from theoxygenator 130, and tubing 230, which carries deoxygenated blood fromthe venous reservoir 122. The oxygenation controller 210 allows theperfusionist to adjust the oxygen levels of the blood sent to thecardioplegia pathway 146. In one embodiment, the oxygenation controller210 includes a dial for adjusting the output oxygenation level and areal-time display for parameters such as oxygen saturation and partialpressure of oxygen (pO₂). In other preferred embodiments, theoxygenation controller 210 may include one or more of a variety ofdifferent input devices, including buttons, knobs, a mouse, a trackball,sliders, touch pads, sensors or touch screens, to control parameters ofthe output blood.

The oxygenation controller 210 mixes oxygenated and deoxygenated bloodin a ratio, which results in a carefully controlled oxygenationsaturation and pO₂ level, and delivers this blood to the cardioplegiasystem 140 by way of the tubing 142. The tubing 142 connects the bloodoutput by the oxygenation controller 210 to the cardioplegia deliverysystem 144. The cardioplegia delivery system 144 then provides thecardioplegia from the oxygenation controller blood mixture andcrystalloid. The cardioplegia is delivered to the coronary circulation116 via the cardioplegia delivery pathway 146.

As shown in FIG. 3, the oxygenation controller 210 may also beencompassed in an integrated cardioplegia delivery apparatus 300. Theintegrated cardioplegia delivery apparatus 300 includes both theoxygenation controller 210 and the cardioplegia delivery system 144.

FIG. 4 depicts another embodiment of an oxygenation controller 400, inwhich the oxygenation control and cardioplegia delivery are integrated.The oxygenation controller 400 includes two inputs: an oxygenated bloodinput 410 and deoxygenated (venous) blood input 415. The oxygenatedblood input 410 receives oxygenated blood directly or indirectly fromthe oxygenator 130. The oxygen partial pressure and saturation levelsare measured by a sensor 420. Pump 430 controls the flow of oxygenatedblood to reservoir 440. As one skilled in the art would appreciate, thepumps may take a variety of forms. For example, a centrifugal pump,roller pump, a piston-based arrangement that may affect flow by theapplication of pressure onto previously described bladder reservoirs, orany now known or later developed device suitable for controlling theflow of fluids may be used.

The deoxygenated blood input 415 directly or indirectly receives bloodthat was collected in the venous reservoir 126. The oxygen partialpressure and saturation levels are measured by sensor 425. The sensor425 is the same or a different type of sensor than used for the sensor420. Pump 435 controls the flow of deoxygenated blood to reservoir 440.The pump 435 is the same or different type of pump as pump 430.

Reservoir 440 holds the mixture of deoxygenated and oxygenated bloodthereby providing a mixed blood supply. As one skilled in the art wouldappreciate, the mixed blood supply may take the form of being held in areservoir, or may stream through a blood line, a line of tubing, or anyother device that may contain a volume of blood. Sensor 450 is the sameor a different type of sensor as sensors 420 and 425. The sensor 450measures the oxygen partial pressure and saturation levels for the bloodin reservoir 440. Pump 460 is the same or different type of pump aspumps 126, 430 or 425. The pump 460 pumps the mixed blood tocardioplegia solution injector 470, which then outputs the resultantperfusate solution for delivery via cannula 146.

Microprocessor 485 receives data from sensors 420, 425 and 450, pumps430, 435 and 460, and perfusion control input 480. The microprocessor485 is a general processor, digital signal processor, applicationspecific integrated circuit, a field programmable gate array, a controlprocessor, an analog circuit, a digital circuit, a network, combinationsthereof or other now known or later developed device for controlling amixing ratio. The microprocessor 485 also controls the output of display490 and the pumps 430, 435 and 460, but separate processors may be usedfor these functions. If included in the oxygenation controller 400, thecardioplegia solution injector 470 may also be controlled by themicroprocessor 485 or a different processor.

Sensors 420 and 425 provide the microprocessor 485 with data about thedeoxygenated and reoxygenated blood received at inputs 410 and 420. Themicroprocessor 485 uses the data received from sensor 420 and 425 tocontrol the rate at which pumps 430 and 435 operate. The sensors may beconstructed using fiberoptics for oximetry readings, continuous bloodgas analysis, or any other method in which real-time blood chemistrylevels, such as pO₂ or oxygen saturation, may be obtained.

Sensor 450 provides the microprocessor 485 with data about the blood mixcontained in the reservoir 440. In alternative embodiments, thereservoir 440 may be replaced with a Y coupling. In such embodiments,the sensor may be located at the output of the Y couple to provide datato the microprocessor 485. The microprocessor then instructs pump 460 tooutput the mixed oxygenated and deoxygenated blood.

Perfusion control 480, such as a memory, processor, data bus, user inputdevice or a data port, allows a perfusionist to control the oxygenpartial pressure and saturation levels. The perfusion control 480provides the microprocessor 485 with the desired parameters. Utilizingthe data received from the sensors 420, 425 and 450, the microprocessor485 can control pumps 430, 435 and 460 to insure that the desiredoxygenation levels of the outputted blood are achieved.

The display 490 is a monitor, CRT, LCD, projector, LED or other nowknown or later developed display device. The display 490 provides visualfeedback to the perfusionist. The display 490 may provide data on theinput and output oxygenation levels, blood flow rates, pressure levelsor combinations thereof. Additional data relating to the blood,crystalloid mixture or other aspects related to the cardioplegiasolution may also be displayed. In a preferred embodiment, the display490 and perfusion control 480 are combined in a single touch screen.

In another embodiment, the cardioplegia solution injector 470 may beseparate from the oxygenation controller 400. As shown in FIG. 2, thecardioplegia delivery system 144 may operate independently from theoxygenation controller 210.

In other embodiments, the reservoir may be omitted, other reservoirs maybe used, and the pumps may be located at a variety of differentlocations. For example, reservoirs or bladders for deoxygenated,oxygenated and mixed blood may be used. Sensors 420, 425 and 450 may beconnected with the deoxygenated, oxygenated and mixed blood reservoirsor bladders, respectively, or a subset thereof. Further, the reservoirsand connected sensors 420, 425, and 450 may all be integrated into adisposable bladder. The flow rate of each of the reservoirs within thedisposable bladder (and consequently the mixture level in mixed bloodreservoir 440) then may be controlled by pumps 430, 435, and 460, whichare in contact with the disposable bladder. The pumping rates of pumps430, 435, and 460 may be controlled by the microprocessor 485, whichreceives data from sensors 420, 425 and 450. Alternatively, separatebladders may be used for each reservoir.

Alternatively, in an embodiment in which the reservoirs are omitted,sensors 420, 425, and 450 may be implemented in Y-shaped tubing, inwhich sensors 420 and 425 are located proximate to the two inputs of theY-shaped tubing and sensor 450 is proximate to the single output of theY-shaped tubing. In this embodiment, the microprocessor 485 may receivedata from sensors 420, 425, and 450 and control pumps 430 and 435 toprovide a desired mixed blood ratio and flow rate of the mixed blood.

Additionally, other sensors may be added to incorporate measurement ofother parameters of the deoxygenated blood, the blood received from theoxygenator, the crystalloid mixture, and the overall mixture provided tothe cardioplegia delivery pathway. The sensors may be in a variety oflocations. For example, sensors may be located in reservoirs, pumps, ortubing. A fewer number of sensors may be used, such as only one sensorat an output of the mix or two sensors at the two inputs without asensor at the output.

In yet another embodiment, the microprocessor may control a timingmechanism that gauges the time frame in which specific levels ofoxygenation (or other parameters) occur. Alarm mechanisms may also beincorporated to send a warning to the perfusionist concerning whetherinput or output blood levels are low, whether the oxygenation levels aretoo high or too low, or whether the crystalloid mixture should beadjusted. The alarms can be controlled by the microprocessor 485 basedon the sensor or other information received and displayed on the display490. Additionally, another microprocessor may control the operation ofthe oxygenation controller 400.

In a further embodiment, the oxygenation system may control allparameters and provide a simple way to dial in oxygen levels to beoutput to the systemic perfusion pathway 132 and cardioplegia deliverypathway 146. In this regard, real-time adjustments may be made through asingle device to provide accurate levels of oxygen provided to brain andheart.

FIG. 5 shows a flowchart for microprocessor control in one embodiment.In act 500, the microprocessor reads a desired partial pressure ofoxygen level, which is input by a user and has been stored in memory. Avariety of memory devices may be used to store data, including memorythat is integrated with the microprocessor. In act 505, the desiredpartial pressure of oxygen level is displayed. In act 510, themicroprocessor reads the actual partial pressure of oxygen level from asensor. This information is displayed in act 515. In acts 520 and 530,the microprocessor reads the partial pressure of oxygen levels of thevenous blood and oxygenated blood, from respective sensors. In acts 525and 535, the respective levels are displayed.

In act 540, the microprocessor compares the desired partial pressure ofoxygen level with the output partial pressure of oxygen level todetermine if they are substantially equal. The microprocessor can be setwith fixed or varying tolerances in assessing this condition. Forexample, the microprocessor may be set such that a 5 percent differencein levels is considered to satisfy the requirement that the levels areequal. If the equality condition is satisfied, the microprocessormaintains the current oxygenated to venous blood flow ratio in act 550,and returns to act 500. If the equality condition is not satisfied, themicroprocessor proceeds to act 560.

In act 560, the microprocessor assesses whether the desired partialpressure of oxygen level is greater or less than the actual outputtedpartial pressure of oxygen level. If the desired level is greater thanthe actual level, the microprocessor directs the pump heads to increasethe oxygenated to venous blood flow ratio in act 570. If the desiredlevel is smaller than the actual level, the microprocessor directs thepump heads to decrease the oxygenated to venous blood flow ratio in act580. After act 570 or 580, the microprocessor returns to act 500.

The flowchart depicted in FIG. 5 is one example of how themicroprocessor can be programmed to provide actual mixtures of thevenous and reoxygenated blood. This process can be performed in avariety of different steps and in a different order. Further, themicroprocessor may also be used to evaluate different blood chemistrylevels, such as pH, partial pressure of CO₂, bicarbonate levels, oroxygen saturation, and provide appropriate mixtures of venous andoxygenated blood to address desired levels of those items. The desiredratio may be altered automatically or manually as a function of time.

It is therefore intended that the foregoing detailed description beregarded as illustrative rather than limiting, and that it be understoodthat it is the following claims, including all equivalents, that areintended to define the spirit and scope of this invention. For example,while embodiments have been disclosed in the context of acardiopulmonary bypass circuit, embodiments may also be used in acatheter lab during an angioplasty procedure, during a heart transplantoperation, or any other environment in which controlled perfusion andcardiac oxygenation is desired. Accordingly, these embodiments may beused for either during cardiac surgery for unstable coronary syndrome orfor long and complex cases involving prolonged surgical times. In suchcases, an embodiment may be used as part and parcel of thecardiopulmonary bypass circuit (heart-lung machine). Alternatively,embodiments may also be used as a free-standing mechanism for thecontrol of perfusion and reoxygenation during percutaneous coronaryintervention (angioplasty and stent procedures).

Further, the blood oxygen levels measured by the sensors may take avariety of forms. For example, the blood oxygen level may comprisepartial pressure of oxygen (pO₂) or the percentage of oxygen saturation(O₂ saturation). Alternatively, the sensors may measure both partialpressure of oxygen (pO₂) and the percentage of oxygen saturation (O₂saturation). In yet another embodiment, the coronary perfusion deviceaddresses blood oxygen levels by considering the total amount of oxygenlevel in the blood (oxygen content). In this regard, an alternativeembodiment may evaluate oxygen content by evaluating pO₂, O₂ saturation,hemoglobin level, and/or the amount of oxygen dissolved in the blood.

1. A coronary perfusion device, comprising: a control input configuredto receive a desired blood oxygen level of mixed blood in a mixed bloodline; a venous blood supply input configured to receive deoxygenatedblood from a patient; an oxygenated blood supply input configured toreceive oxygenated blood from an oxygenator; the mixed blood lineconnected with said venous blood supply input and said oxygenated bloodsupply input and configured so as to output the mixed blood, the mixedblood comprising a mixture of deoxygenated blood from the venous bloodsupply input and oxygenated blood from the oxygenated blood supplyinput; a mixed blood sensor configured to measure blood oxygen levels inthe mixed blood line; and a microprocessor that is programmed to receivedata from said control input and said mixed blood sensor; wherein themicroprocessor is programmed to control the mixing of blood as afunction of the desired blood oxygen level; and wherein the mixed bloodline provides coronary perfusion to the patient.
 2. The coronaryperfusion device of claim 1 further comprising: a venous blood sensorconfigured to measure oxygen levels of the deoxygenated blood; and anoxygenated blood sensor configured to measure oxygen levels of theoxygenated blood; wherein the microprocessor is further programmed toreceive data from said venous blood sensor and said oxygenated bloodsensor.
 3. The coronary perfusion device of claim 1 further comprising:a venous blood pump connected with the venous blood supply input andconfigured to adjust flow of venous blood; and an oxygenated blood pumpconnected with the oxygenated blood supply input and configured toadjust flow of oxygenated blood.
 4. The coronary perfusion device ofclaim 1, wherein the oxygen levels are measurements of partial pressureof oxygen in the blood.
 5. The coronary perfusion device of claim 1further comprising a mixed blood supply connected with said mixed bloodline, said mixed blood supply configured to hold mixed blood.
 6. Thecoronary perfusion device of claim 1 further comprising a mixed bloodsupply having a first input connected with said oxygenated blood input,a second input connected with said venous blood input, and outputconnected with said mixed blood line.
 7. The coronary perfusion deviceof claim 1 further comprising a mixed blood pump connected with saidmixed blood line.
 8. The coronary perfusion device of claim 1 furthercomprising a display connected with said microprocessor and configuredto display blood oxygen level data.
 9. The coronary perfusion device ofclaim 1 wherein the control input comprises a touch screen.
 10. Thecoronary perfusion device of claim 9 wherein the touch screen isconfigured to receive a tactile input and display blood oxygen leveldata.
 11. The coronary perfusion device of claim 1 wherein the controlinput is a dial.
 12. The coronary perfusion device of claim 1 whereinthe mixed blood sensor measures partial pressure of oxygen in blood. 13.The coronary perfusion device of claim 2 wherein the venous blood sensorand oxygenated blood sensor measure partial pressure of oxygen in blood.